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A novel strategy for the stereospecific Pd-catalyzed acylative cross-coupling of enantiomerically enriched alkylboron compounds has been developed. The protocol features an extremely high level of enantiospecificity to allow facile access to synthetically challenging and valuable chiral ketones and carboxylic acid derivatives. The use of a sterically encumbered and electron-rich phosphine ligand proved to be crucial for the success of the reaction. Furthermore, on the basis of experimental and computational studies, a unique mechanism for the transmetalation, assisted by the noncovalent interactions of the C(sp3)-based organoboron reagent, has been identified.
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Occupational attainment, which represents middle-age cognitive activities, is a known proxy marker of cognitive reserve for Alzheimer's disease. Previous genome-wide association studies have identified numerous genetic variants and revealed the genetic architecture of educational attainment, another marker of cognitive reserve. However, the genetic architecture and heritability for occupational attainment remain elusive. We performed a large-scale genome-wide association study of occupational attainment with 248â847 European individuals from the UK Biobank using the proportional odds logistic mixed model method. In this analysis, we defined occupational attainment using the classified job levels formulated in the UK Standard Occupational Classification system considering the individual professional skill and academic level. We identified 30 significant loci (P < 5 × 10-8); 12 were novel variants, not associated with other traits. Among them, four lead variants were associated with genes expressed in brain tissues by expression quantitative trait loci mapping from 10 brain regions: rs13002946, rs3741368, rs11654986 and rs1627527. The single nucleotide polymorphism-based heritability was estimated to be 8.5% (standard error of the mean = 0.004) and partitioned heritability was enriched in the CNS and brain tissues. Genetic correlation analysis showed shared genetic backgrounds between occupational attainment and multiple traits, including education, intelligence, leisure activities, life satisfaction and neuropsychiatric disorders. In two-sample Mendelian randomization analysis, we demonstrated that high occupation levels were associated with reduced risk for Alzheimer's disease [odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.65-0.92 in inverse variance weighted method; OR = 0.73, 95% CI = 0.57-0.92 in the weighted median method]. This causal relationship between occupational attainment and Alzheimer's disease was robust in additional sensitivity analysis that excluded potentially pleiotropic single nucleotide polymorphisms (OR = 0.72, 95% CI = 0.57-0.91 in the inverse variance weighted method; OR = 0.72, 95% CI = 0.53-0.97 in the weighted median method). Multivariable Mendelian randomization confirmed that occupational attainment had an independent effect on the risk for Alzheimer's disease even after taking educational attainment into account (OR = 0.72, 95% CI = 0.54-0.95 in the inverse variance weighted method; OR = 0.68, 95% CI = 0.48-0.97 in the weighted median method). Overall, our analyses provide insights into the genetic architecture of occupational attainment and demonstrate that occupational attainment is a potential causal protective factor for Alzheimer's disease as a proxy marker of cognitive reserve.
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Doença de Alzheimer , Reserva Cognitiva , Ocupações , Doença de Alzheimer/genética , Biomarcadores , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
In wireless sensor networks, tree-based routing can achieve a low control overhead and high responsiveness by eliminating the path search and avoiding the use of extensive broadcast messages. However, existing approaches face difficulty in finding an optimal parent node, owing to conflicting performance metrics such as reliability, latency, and energy efficiency. To strike a balance between these multiple objectives, in this paper, we revisit a classic problem of finding an optimal parent node in a tree topology. Our key idea is to find the best parent node by utilizing empirical data about the network obtained through Q-learning. Specifically, we define a state space, action set, and reward function using multiple cognitive metrics, and then find the best parent node through trial and error. Simulation results demonstrate that the proposed solution can achieve better performance regarding end-to-end delay, packet delivery ratio, and energy consumption compared with existing approaches.
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Algoritmos , Tecnologia sem Fio , Reprodutibilidade dos Testes , Simulação por ComputadorRESUMO
Many applications are able to obtain enriched information by employing a wireless multimedia sensor network (WMSN) in industrial environments, which consists of nodes that are capable of processing multimedia data. However, as many aspects of WMSNs still need to be refined, this remains a potential research area. An efficient application needs the ability to capture and store the latest information about an object or event, which requires real-time multimedia data to be delivered to the sink timely. Motivated to achieve this goal, we developed a new adaptive QoS routing protocol based on the (m,k)-firm model. The proposed model processes captured information by employing a multimedia stream in the (m,k)-firm format. In addition, the model includes a new adaptive real-time protocol and traffic handling scheme to transmit event information by selecting the next hop according to the flow status as well as the requirement of the (m,k)-firm model. Different from the previous approach, two level adjustment in routing protocol and traffic management are able to increase the number of successful packets within the deadline as well as path setup schemes along the previous route is able to reduce the packet loss until a new path is established. Our simulation results demonstrate that the proposed schemes are able to improve the stream dynamic success ratio and network lifetime compared to previous work by meeting the requirement of the (m,k)-firm model regardless of the amount of traffic.
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To improve the packet delivery ratio in wireless sensor networks, many approaches such as multipath, opportunistic, and learning-based routing protocols have been proposed. However, the performance of the existing protocols are degraded under long-hop wireless sensor networks because the additional overhead is proportional to the number of hops. To deal with the overhead, we propose an opportunistic multipath routing that forecasts the required number of paths, as well as bifurcation based on opportunistic routing according to the reliability requirement. In the proposed scheme, an intermediate node is able to select a different node for each transmission and to handle path failure adaptively. Through a performance evaluation, we demonstrate that the proposed scheme achieves a higher packet delivery ratio and reduces the energy consumption by at least approximately 33% and up to approximately 65% compared with existing routing protocols, under the condition of an 80% link success ratio in the long-hop sensor network.
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Before discovering meaningful knowledge from big data systems, it is first necessary to build a data-gathering infrastructure. Among many feasible data sources, wireless sensor networks (WSNs) are rich big data sources: a large amount of data is generated by various sensor nodes in large-scale networks. However, unlike typical wireless networks, WSNs have serious deficiencies in terms of data reliability and communication owing to the limited capabilities of the nodes. Moreover, a considerable amount of sensed data are of no interest, meaningless, and redundant when a large number of sensor nodes is densely deployed. Many studies address the existing problems and propose methods to overcome the limitations when constructing big data systems with WSN. However, a published paper that provides deep insight into this research area remains lacking. To address this gap in the literature, we present a comprehensive survey that investigates state-of-the-art research work on introducing WSN in big data systems. Potential applications and technical challenges of networks and infrastructure are presented and explained in accordance with the research areas and objectives. Finally, open issues are presented to discuss promising directions for further research.
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BACKGROUND & AIMS: Early-onset gastric cancer, which develops in patients younger than most gastric cancers, is usually detected at advanced stages, has diffuse histologic features, and occurs more frequently in women. We investigated somatic genomic alterations associated with the unique characteristics of sporadic diffuse gastric cancers (DGCs) from younger patients. METHODS: We conducted whole exome and RNA sequence analyses of 80 resected DGC samples from patients 45 years old or younger in Korea. Patients with pathogenic germline mutations in CDH1, TP53, and ATM were excluded from the onset of this analysis, given our focus on somatic alterations. We used MutSig2CV to evaluate the significance of mutated genes. We recruited 29 additional early-onset Korean DGC samples and performed SNP6.0 array and targeted sequencing analyses of these 109 early-onset DGC samples (54.1% female, median age, 38 years). We compared the SNP6.0 array and targeted sequencing data of the 109 early-onset DGC samples with those from diffuse-type stomach tumor samples collected from 115 patients in Korea who were 46 years or older (late onset) at the time of diagnosis (controls; 29.6% female, median age, 67 years). We compared patient survival times among tumors from different subgroups and with different somatic mutations. We performed gene silencing of RHOA or CDH1 in DGC cells with small interfering RNAs for cell-based assays. RESULTS: We identified somatic mutations in the following genes in a significant number of early-onset DGCs: the cadherin 1 gene (CDH1), TP53, ARID1A, KRAS, PIK3CA, ERBB3, TGFBR1, FBXW7, RHOA, and MAP2K1. None of 109 early-onset DGC cases had pathogenic germline CDH1 mutations. A higher proportion of early-onset DGCs had mutations in CDH1 (42.2%) or TGFBR1 (7.3%) compared with control DGCs (17.4% and 0.9%, respectively) (P < .001 and P = .014 for CDH1 and TGFBR1, respectively). In contrast, a smaller proportion of early-onset DGCs contained mutations in RHOA (9.2%) than control DGCs (19.1%) (P = .033). Late-onset DGCs in The Cancer Genome Atlas also contained less frequent mutations in CDH1 and TGFBR1 and more frequent RHOA mutations, compared with early-onset DGCs. Early-onset DGCs from women contained significantly more mutations in CDH1 or TGFBR1 than early-onset DGCs from men. CDH1 alterations, but not RHOA mutations, were associated with shorter survival times in patients with early-onset DGCs (hazard ratio, 3.4; 95% confidence interval, 1.5-7.7). RHOA activity was reduced by an R5W substitution-the RHOA mutation most frequently detected in early-onset DGCs. Silencing of CDH1, but not RHOA, increased migratory activity of DGC cells. CONCLUSIONS: In an integrative genomic analysis, we found higher proportions of early-onset DGCs to contain somatic mutations in CDH1 or TGFBR1 compared with late-onset DGCs. However, a smaller proportion of early-onset DGCs contained somatic mutations in RHOA than late-onset DGCs. CDH1 alterations, but not RHOA mutations, were associated with shorter survival times of patients, which might account for the aggressive clinical course of early-onset gastric cancer. Female predominance in early-onset gastric cancer may be related to relatively high rates of somatic CDH1 and TGFBR1 mutations in this population.
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Idade de Início , Caderinas/genética , Proteínas Serina-Treonina Quinases/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Neoplasias Gástricas/genética , Proteína rhoA de Ligação ao GTP/genética , Adulto , Antígenos CD , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Receptor do Fator de Crescimento Transformador beta Tipo I , República da Coreia , Fatores Sexuais , Adulto JovemRESUMO
OBJECTIVE: There is growing interest in the use of cuttlefish bone (CB) as a bone graft material. Silicon (Si) plays an important role in bone formation and calcification. This study aimed to prepare Si-substituted CB-derived hydroxyapatite (Si-CB-HAp) using a natural CB to improve the bioactivity for bone formation. MATERIALS AND METHODS: We prepared Si-HAp from CB (Si-CB-HAp) using a hydrothermal and solvothermal method. The microstructure and chemical composition were characterized by scanning electron microscope (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectrometer (EDS). The bioactivity of the Si-CB-HAp was evaluated using human mesenchymal stem cells. Furthermore, the in vivo bone regeneration efficiency was evaluated using a rabbit calvarial defect model. RESULTS: Our results show that the Si content was 0.77 wt% in Si-CB-HAp, and its original microstructure was conserved. The presence of Si was shown to enhance cell proliferation and early cellular attachment of human mesenchymal stem cells. Additionally, results of alkaline phosphatase activity and real-time PCR for osteoblast marker genes show that Si substitution into CB-HAp enhanced osteoblast differentiation. In addition, in vivo bone defect healing experiments show that the formation of bone with Si-CB-HAp is higher than that with CB-HAp. CONCLUSION: These results indicate that Si-CB-HAp may potentially be used as a bone graft material to enhance bone healing.
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Materiais Biocompatíveis/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Durapatita/administração & dosagem , Animais , Adesão Celular , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Decapodiformes , Humanos , Células-Tronco MesenquimaisRESUMO
Wireless Body Area Networks (WBANs) have attracted research interests from the community, as more promising healthcare applications have a tendency to employ them as underlying network technology. While taking design issues, such as small size hardware as well as low power computing, into account, a lot of research has been proposed to accomplish the given tasks in WBAN. However, since most of the existing works are basically developed by assuming all nodes in the static state, these schemes therefore cannot be applied in real scenarios where network topology between sensor nodes changes frequently and unexpectedly according to human moving behavior. However, as far as the authors know, there is no survey paper to focus on research challenges for mobility support in WBAN yet. To address this deficiency, in this paper, we present the state-of-the-art approaches and discuss the important features of related to mobility in WBAN. We give an overview of mobility model and categorize the models as individual and group. Furthermore, an overview of networking techniques in the recent literature and summary are compiled for comparison in several aspects. The article also suggests potential directions for future research in the field.
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Recently, various unicast routing protocols have been proposed to deliver measured data from the sensor node to the sink node within the predetermined deadline in wireless sensor networks. In parallel with their approaches, some applications demand the specific service, which is based on broadcast to all nodes within the deadline, the feasible real-time traffic model and improvements in energy efficiency. However, current protocols based on either flooding or one-to-one unicast cannot meet the above requirements entirely. Moreover, as far as the authors know, there is no study for the real-time broadcast protocol to support the application-specific traffic model in WSN yet. Based on the above analysis, in this paper, we propose a new (m, k)-firm-based Real-time Broadcast Protocol (FRBP) by constructing a broadcast tree to satisfy the (m, k)-firm, which is applicable to the real-time model in resource-constrained WSNs. The broadcast tree in FRBP is constructed by the distance-based priority scheme, whereas energy efficiency is improved by selecting as few as nodes on a tree possible. To overcome the unstable network environment, the recovery scheme invokes rapid partial tree reconstruction in order to designate another node as the parent on a tree according to the measured (m, k)-firm real-time condition and local states monitoring. Finally, simulation results are given to demonstrate the superiority of FRBP compared to the existing schemes in terms of average deadline missing ratio, average throughput and energy consumption.
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Intensive research studies have revealed that fungal decolorization of dye wastewater is a promising replacement for the current process of dye wastewater decolorization. The authors isolated an Aspergillus sp. from the effluent of a textile industry area in Korea and assessed the effects of a variety of operational parameters on the decolorization of methyl red (MR) by this strain of Aspergillus sp. This Aspergillus sp. was then immobilized by entrapment in several polymeric matrices and the effects of operational conditions on MR decolorization were investigated again. The optimal decolorization activity of this Aspergillus sp. was observed in 1% glucose at a temperature of 37 °C and pH of 6.0. Furthermore, stable decolorization efficiency was observed when fungal biomass was immobilized into alginate gel during repeated batch experiment. These results suggest that the Aspergillus sp. isolated in Korea could be used to treat industrial wastewaters containing MR dye.
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Aspergillus/metabolismo , Compostos Azo/metabolismo , Reatores Biológicos , Poluentes Químicos da Água/metabolismo , Alginatos , Aspergillus/química , Aspergillus/efeitos dos fármacos , Compostos Azo/química , Células Imobilizadas , Glucose/metabolismo , Glucose/farmacologia , Ácido Glucurônico , Ácidos Hexurônicos , Concentração de Íons de Hidrogênio , Polímeros , Temperatura , Poluentes Químicos da Água/químicaRESUMO
OBJECTIVES: Fibrin clots play an important role in bone tissue regeneration. This study aimed at improving the fibrin-clotting rate by coating the surface of biphasic calcium phosphate (BCP) granules with fibrinogen (FNG). METHODS AND MATERIALS: FNG was coated on the BCP surface using an adsorption and freeze-drying method. The surface morphology of FNG-adsorbed BCP (FNG-BCP) was characterized using scanning electron microscopy (SEM), and the stability of the adsorbed FNG evaluated by gel electrophoresis and circular dichroism (CD) analysis. The biocompatibility of FNG-BCP was evaluated in vitro using human mesenchymal stem cells, and in vivo bone-healing efficiency determined using a rabbit calvarial bone defect model. RESULTS: SEM studies showed numerous irregularly distributed FNG fractions adsorbed onto the surface of BCP granules. Gel electrophoresis, CD analysis, and in vitro coagulation results showed that the adsorbed FGN maintained its native protein structure and clotting properties. Biocompatibility experiments showed that cell proliferation and adhesion were improved in cells cultivated on the FNG-BCP granules. After surgical implantation into the bone defects, the FNG-BCP granules coagulated at the defect site by reacting with the blood discharged from the surgical site tissue. In addition, at 8 weeks, the volume of FNG40-BCP (P = 0.012) was significantly higher than that of BCP alone in the newly formed bone. CONCLUSIONS: These results indicate that self-coagulating FNG-CBP granules may have the potential to be used as a bone substitute for enabling effective bone repair through rapid fibrin-clot formation.
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Adsorção , Coagulação Sanguínea , Substitutos Ósseos/metabolismo , Fibrinogênio/metabolismo , Consolidação da Fratura , Fraturas Ósseas/terapia , Hidroxiapatitas/metabolismo , Animais , Materiais Biocompatíveis/metabolismo , Dicroísmo Circular , Eletroforese , Teste de Materiais , Microscopia Eletrônica de Varredura , Ligação Proteica , Coelhos , Propriedades de Superfície , Resultado do TratamentoRESUMO
OBJECTIVE: This study aimed to optimize the fibrinogen concentration in fibrin and atelocollagen (AT-COL) (fibrin/AT-COL) composite gel for improving bone regeneration. METHODS AND MATERIALS: The fibrin/AT-COL composite gels were fabricated using various fibrinogen concentrations, and the microstructure and mechanical properties of the resulting composite gels analyzed. The cytocompatibility of the composite gels was examined using human mesenchymal stem cell (hMSCs). Furthermore, in nine rabbits, the in vivo bone regeneration efficiency was evaluated using a rabbit calvarial defects model at 2 weeks (n = 3), 4 weeks (n = 3), and 8 weeks (n = 3). RESULTS: Scanning electron microscopy analysis revealed the formation of a fibrin layer matrix and collagen fibril networks. The composite gel containing 40 mg/ml fibrinogen showed a densely packed fibrin matrix and displayed superior mechanical properties. Cells cultured in the composite gels prepared with 5-20 mg/ml fibrinogen appeared elongated, with a spindle-like morphology. At a higher fibrinogen concentration (40 mg/ml), many cells were rounded and showed limited viability. In an in vivo study, at 8 weeks, the volume of fibrin/AT-COL gel (P = 0.02) was significantly higher than that of fibrin gel alone in the newly formed bone. Histological analysis revealed more islands of newly formed bone filling the central area of the defect in the fibrin/AT-COL gel-implanted animals. CONCLUSION: Our results demonstrate that optimization of the fibrinogen content of fibrin/AT-COL composites should be beneficial for bone tissue engineering.
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Colágeno , Fibrina , Fibrinogênio , Géis , Animais , Materiais Biocompatíveis/química , Regeneração Óssea , Proliferação de Células , Células Cultivadas , Colágeno/química , Fibrina/química , Fibrinogênio/química , Géis/química , Humanos , Células-Tronco Mesenquimais/citologia , Microscopia Eletrônica de Varredura , Modelos Animais , Coelhos , Crânio , Engenharia Tecidual , Alicerces Teciduais/química , Microtomografia por Raio-XRESUMO
Angiogenesis is an indispensable mechanism in cancer progression, as cancer cells need to establish blood vessels to supply oxygen and nutrients. Extracellular vesicles (EVs) derived from cancer cells act as messengers in the tumor microenvironment and induce resistance to anti-angiogenic cancer treatment. EVs can be classified into two categories: exosomes and microvesicles (MVs). Although exosomes are involved in angiogenesis, the role of MVs in angiogenesis and cancer progression remains unclear. CD133 plays a key role in MV formation and oncoprotein trafficking. In this study, we investigated the role of CD133-containing MVs derived from colorectal cancer (CRC) in angiogenesis and cancer progression. CRC-derived MVs were incorporated into endothelial cells and increased the mesh area and tube length of endothelial cells. CD133-containing MVs also stimulate vessel sprouting in endothelial cell spheroids and mouse thoracic aortas. However, MVs derived from CD133-knockdown CRC cells exerted a limited effect on tube formation and vessel sprouting. CD133-containing MVs induced angiogenesis through p38 activation and angiogenesis induced by CD133-containing MVs was insensitive to the anti-vascular endothelial growth factor antibody bevacizumab. Survival analysis revealed that high expression level of CD133 correlated with poor prognosis in patients with metastatic CRC. These findings suggest that CD133-containing MVs act as key regulators of angiogenesis and are related to the prognosis of CRC patients.
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This study demonstrated the effect of differences in the exterior of erosion control dams (ECDs) on humans. We recruited 34 university students. Participants sat 1.4 m away from the display while wearing a device for measuring heart rate (HR) and heart rate variability. They (i) took a rest while viewing a gray screen for one minute; (ii) viewed a randomly displayed image of one of the three ECDs' images for one minute; (iii) filled out questionnaires (using the semantic differential method and a profile of mood states) for five minutes; and (iv) took a rest to wash out residual sensitivity for five minutes. The process was repeated three times with three different ECD images. No significant difference was found between the participants' HRs measured before and while viewing the images of the three ECDs with different exterior materials, although the HRs were significantly reduced when viewing the wood-attached ECD compared with the concrete-exposed ECD. Participants perceived the concrete-exposed and stone-attached ECDs artificially, while they felt the wood-attached ECD naturally. In addition, the vigor score was significantly increased while total mood disturbance was significantly decreased when viewing the wood-attached ECD. However, there were no significant differences in other indicators, and participants' responses to the exteriors of the ECDs were positive overall. Our findings show that people do not physiologically and psychologically perceive ECDs negatively. Therefore, securing stability against sedimentary disasters should be a priority before using the landscape elements of an ECD.
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Frequência Cardíaca , Humanos , Masculino , Feminino , Frequência Cardíaca/fisiologia , Adulto Jovem , Adulto , Afeto/fisiologia , Inquéritos e Questionários , Conservação dos Recursos NaturaisRESUMO
Evidence for adaptation of human skin color to regional ultraviolet radiation suggests shared and distinct genetic variants across populations. However, skin color evolution and genetics in East Asians are understudied. We quantified skin color in 48,433 East Asians using image analysis and identified associated genetic variants and potential causal genes for skin color as well as their polygenic interplay with sun exposure. This genome-wide association study (GWAS) identified 12 known and 11 previously unreported loci and SNP-based heritability was 23-24%. Potential causal genes were determined through the identification of nonsynonymous variants, colocalization with gene expression in skin tissues, and expression levels in melanocytes. Genomic loci associated with pigmentation in East Asians substantially diverged from European populations, and we detected signatures of polygenic adaptation. This large GWAS for objectively quantified skin color in an East Asian population improves understanding of the genetic architecture and polygenic adaptation of skin color and prioritizes potential causal genes.
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Estudo de Associação Genômica Ampla , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Pigmentação da Pele , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adaptação Fisiológica/genética , Mapeamento Cromossômico , Herança Multifatorial/genética , Locos de Características Quantitativas/genética , Pigmentação da Pele/genética , Raios Ultravioleta , População do Leste AsiáticoRESUMO
Metabolic syndrome (MetS) is a complex hereditary condition comprising various metabolic traits as risk factors. Although the genetics of individual MetS components have been investigated actively through large-scale genome-wide association studies, the conjoint genetic architecture has not been fully elucidated. Here, we performed the largest multivariate genome-wide association study of MetS in Europe (nobserved = 4,947,860) by leveraging genetic correlation between MetS components. We identified 1,307 genetic loci associated with MetS that were enriched primarily in brain tissues. Using transcriptomic data, we identified 11 genes associated strongly with MetS. Our phenome-wide association and Mendelian randomization analyses highlighted associations of MetS with diverse diseases beyond cardiometabolic diseases. Polygenic risk score analysis demonstrated better discrimination of MetS and predictive power in European and East Asian populations. Altogether, our findings will guide future studies aimed at elucidating the genetic architecture of MetS.
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Hyperuricemia is an essential causal risk factor for gout and is associated with cardiometabolic diseases. Given the limited contribution of East Asian ancestry to genome-wide association studies of serum urate, the genetic architecture of serum urate requires exploration. A large-scale cross-ancestry genome-wide association meta-analysis of 1,029,323 individuals and ancestry-specific meta-analysis identifies a total of 351 loci, including 17 previously unreported loci. The genetic architecture of serum urate control is similar between European and East Asian populations. A transcriptome-wide association study, enrichment analysis, and colocalization analysis in relevant tissues identify candidate serum urate-associated genes, including CTBP1, SKIV2L, and WWP2. A phenome-wide association study using polygenic risk scores identifies serum urate-correlated diseases including heart failure and hypertension. Mendelian randomization and mediation analyses show that serum urate-associated genes might have a causal relationship with serum urate-correlated diseases via mediation effects. This study elucidates our understanding of the genetic architecture of serum urate control.
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Estudo de Associação Genômica Ampla , Hiperuricemia , Ácido Úrico , Humanos , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Gota/genética , Gota/sangue , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/sangue , Hipertensão/genética , Hipertensão/sangue , Hiperuricemia/genética , Hiperuricemia/sangue , Análise da Randomização Mendeliana , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Transcriptoma , Ácido Úrico/sangueRESUMO
Educational attainment (EduYears), a heritable trait often used as a proxy for cognitive ability, is associated with various health and social outcomes. Previous genome-wide association studies (GWASs) on EduYears have been focused on samples of European (EUR) genetic ancestries. Here we present the first large-scale GWAS of EduYears in people of East Asian (EAS) ancestry (n = 176,400) and conduct a cross-ancestry meta-analysis with EduYears GWAS in people of EUR ancestry (n = 766,345). EduYears showed a high genetic correlation and power-adjusted transferability ratio between EAS and EUR. We also found similar functional enrichment, gene expression enrichment and cross-trait genetic correlations between two populations. Cross-ancestry fine-mapping identified refined credible sets with a higher posterior inclusion probability than single population fine-mapping. Polygenic prediction analysis in four independent EAS and EUR cohorts demonstrated transferability between populations. Our study supports the need for further research on diverse ancestries to increase our understanding of the genetic basis of educational attainment.
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Sucesso Acadêmico , População do Leste Asiático , Humanos , Escolaridade , Estudo de Associação Genômica Ampla , Herança Multifatorial/genética , População BrancaRESUMO
Creativity is known to be heritable and exhibits familial aggregation with psychiatric disorders; however, the complex nature of their relationship has not been well-established. In the present study, we demonstrate that using an expanded and validated machine learning (ML)-based phenotyping of occupational creativity (OC) can allow us to further understand the trait of creativity, which was previously difficult to define and study. We conducted the largest genome-wide association study (GWAS) on OC with 241,736 participants from the UK Biobank and identified 25 lead variants that have not yet been reported and three candidate causal genes that were previously associated with educational attainment and psychiatric disorders. We found extensive genetic overlap between OC and psychiatric disorders with mixed effect direction through various post-GWAS analyses, including the bivariate causal mixture model. In addition, we discovered a strongly genetic correlation between our original GWAS and the GWAS adjusted for education years (rg = 0.95). Our GWAS analysis via ML-based phenotyping contributes to the understanding of the genetic architecture of creativity, which may inform genetic discovery and genetic prediction in human cognition and psychiatric disorders.